Proton pump inhibitors (or “PPIs”) are a class of pharmaceutical compounds that inhibit gastric acid secretions by inhibiting H+/K+ adenosine triphosphate, an enzyme present in parietal cells found in the gastric lining of the stomach. H+/K+ adenosine triphosphate is variously referred to as an “acid pump” or “proton pump” and examples of PPI's include lansoprazole, omeprazole, and pantoprazole. PPIs rapidly degrade in acidic environments and therefore, dosage forms containing PPIs generally are designed to protect the PPI from the acidic environment of the stomach. Specifically, such dosage forms are designed such that a single dose of the PPI is released in the upper small intestine where the PPI can be absorbed.
Peak plasma concentrations for PPIs typically occur within 1-3 hours after ingestion, and the half-life of such drugs is generally short, usually less than 2 hours. Notwithstanding the relatively quick peak plasma levels and half-lives associated with PPIs, a prolonged therapeutic effect is attained regardless of their relatively short pharmacokinetic half life. In fact, the therapeutic effect of PPIs does not directly correlate with serum concentrations of these drugs. Accordingly, patients on PPI therapy are generally only required to take a single dosage form containing a daily dose of a PPI, usually prior to breakfast. Unfortunately, although the therapeutic effect of these drugs is longer than would otherwise be anticipated, some patients on PPI therapy experience a nocturnal break through event where the secretory activity of the proton pumps return. As a result, the acidity in the stomach increases and the discomfort associated with the increased acid returns.
Unfortunately, it currently does not appear that there is a solution to the nocturnal breakthrough phenomenon associated with PPIs. There is therefore a need for a dosage form containing a PPI that reliably can provide a full day of therapeutic effect while being administered on a once a day basis.